Correlations of Structure and Dynamics in an Aging Colloidal Glass

We study concentrated colloidal suspensions, a model system which has a glass transition. Samples in the glassy state show aging, in that the motion of the colloidal particles slows as the sample ages from an initial state. We study the relationship between the static structure and the slowing dynamics, using confocal microscopy to follow the three-dimensional motion of the particles. The structure is quantified by considering tetrahedra formed by quadruplets of neighboring particles. We find that while the sample clearly slows down during aging, the static properties as measured by tetrahedral quantities do not vary. However, a weak correlation between tetrahedron shape and mobility is observed, suggesting that the structure facilitates the motion responsible for the sample aging.Comment: Submitted to Solid State Communication

A Systematic Review of Semantic Feature Analysis Therapy Studies for Aphasia

Purpose : The purpose of this study was to review treatment studies of semantic feature analysis (SFA) for persons with aphasia . The review documents how SFA is used, appraises the quality of the included studies and evaluates the efficacy of SFA. Methods : The following electronic databases were systematically searched (last search February 2017) : Academic Search Complete; CINAHL Plus; E -journals; Health Policy Reference Centre; MEDLINE; PsycART ICLES; PsycINFO; and SocINDEX. The quality of the included studies was rated. Clinical efficacy was determined by calculating effect sizes ( Cohen’s d ) or percent of non-overlapping data when d could not be calculated. Results: Twenty -one studies were reviewed reporting on 55 persons with aphasia. SFA was used in six different types of studies: confrontation naming of nouns, of verbs , connected speech /discourse, group, multilingual and studies where SFA was compared with other approaches . The quality of included studies was high [ Single Case Experimental Design Scale (SCED S) average (range) =9.55 ( 8.0- 11 )]. Naming of trained items improved for 45 participants ( 81.82%). Effect sizes indicated there was a small treatment effect. Conclusions: SFA leads to p ositive outcomes despite the variability of treatment procedures, dosage, duration and variations to the traditional SFA protocol. Further research is warranted to examine the efficacy of SFA and generalization effects in larger controlled studies

Discovery of Inhibitors for Proliferating Cell Nuclear Antigen Using a Computational-Based Linked-Multiple-Fragment Screen

Proliferating cell nuclear antigen (PCNA) is a central factor in DNA replication and repair pathways that plays an essential role in genome stability. The functional roles of PCNA are mediated through an extensive list of protein-protein interactions, each of which transmits specific information in protein assemblies. The flexibility at the PCNA-protein interaction interfaces offers opportunities for the discovery of functionally selective inhibitors of DNA repair pathways. Current fragment-based drug design methodologies can be limited by the flexibility of protein interfaces. These factors motivated an approach to defining compounds that could leverage previously identified subpockets on PCNA that are suitable for fragment-binding sites. Methodologies for screening multiple connected fragment-binding events in distinct subpockets are deployed to improve the selection of fragment combinations. A flexible backbone based on; N; -alkyl-glycine amides offers a scaffold to combinatorically link multiple fragments for in silico screening libraries that explore the diversity of subpockets at protein interfaces. This approach was applied to discover new potential inhibitors of DNA replication and repair that target PCNA in a multiprotein recognition site. The screens of the libraries were designed to computationally filter ligands based upon the fragments and positions to <1%, which were synthesized and tested for direct binding to PCNA. Molecular dynamics simulations also revealed distinct features of these novel molecules that block key PCNA-protein interactions. Furthermore, a Bayesian classifier predicted 15 of the 16 new inhibitors to be modulators of protein-protein interactions, demonstrating the method's utility as an effective screening filter. The cellular activities of example ligands with similar affinity for PCNA demonstrate unique properties for novel selective synergy with therapeutic DNA-damaging agents in drug-resistant contexts

Recommendations for Science-Based Safety Assessment of Genetically Modified (GM) Plants for Food and Feed Uses

Since the commercial introduction of genetically modified (GM) plants in agriculture over two decades ago, technology developers and regulatory authorities have gained significant experience in assessing their safety based on assessing potential impact to humans, animals and the environment.  Over 3500 independent regulatory agency reviews have positively concluded on the safety of GM plants for food and feed. Yet, divergent and increased regulatory requirements have led to delayed and asynchronous approvals, and have restricted access to innovative products for farmers and consumers. With accumulated knowledge from safety assessments conducted so far, an enhanced understanding of plant genomes, and a history of safe use, it is time to re-evaluate the current approaches to the regulation of GM plants used for food and feed.  A stepwise approach using weight-of-evidence should be sufficient for the safety assessment of newly expressed proteins in GM plants.  A set of core studies including molecular characterization, expression and characterization of the newly expressed proteins (or other expression product), and safety assessment of the introduced protein are appropriate to characterize the product and assess safety.  Using data from core studies, and employing a “problem formulation” approach, the need for supplementary hypothesis-driven or case-by-case studies can be determined.  Employing this approach for the evaluation of GM plants will remove regulatory data requirements that do not provide value to the safety assessment and provide a consistent framework for global regulation. doi: 10.21423/jrs-v09i1water

Performing Arts Session

The music department is proud to present the research of its students through performance. Most of these students are majoring or minoring in music and spend considerable time developing their technique and mastering the art of expression. Each performance is informed by significant research on the composer and the composition. These performances will feature the following students and will include classical guitar, arias, art song, instrumental solo pieces and instrumental chamber music. The performances will appear in no particular order. Please stop by and enjoy this offering of classical music in the lively acoustic and glorious backdrop of the Weisman Museum of Art. The musicians will be performing in the upper gallery

Core and Supplementary Studies to Assess the Safety of Genetically Modified (GM) Plants Used for Food and Feed

Genetically modified (GM) plants used for food and feed have an established history of safe use over more than 25 years of their commercialization. Developers and regulatory authorities have accumulated extensive experience in evaluating their safety over time. The studies required for the safety assessment of GM plants used for food and feed should now be re-defined to leverage this experience and increased scientific knowledge. This paper, a companion paper for Waters et al. also published in this issue, presents a systematic approach for the safety assessment of newly expressed proteins (NEPs) in GM plants by evaluating the two components of risk: hazard and exposure. Although the paper focuses on NEPs, the principles presented could also apply to other expression products that do not result in a NEP. A set of core studies is recommended, along with supplementary studies, if needed, to evaluate whether the GM plant poses risk. Core studies include molecular and protein characterization and hazard identification encompassing toxicity and allergenicity. In the absence of hazard, core studies are sufficient to conclude that GM plants are as safe as their conventional counterparts. Depending on the GM trait and intended use, supplementary studies should be performed to characterize hazard and exposure when a hazard is identified. Problem formulation should be used to identify hypothesis-driven supplementary studies. Acute toxicity studies, compositional assessment, and dietary exposure assessment are recommended to be hypothesis-driven supplementary studies. Further discussion on the current food and feed safety assessment landscape for GM plants and the use of problem formulation as a tool for identifying supplementary studies can be found in the companion paper [62]. doi: 10.21423/jrs-v09i1brun